Neurotrophic factors are polypeptides that are required for the development of the nervous system. The first neurotrophic factor discovered, nerve growth factor (NGF), is now known to be a part of a large family of growth factors, which also includes brain-derived neurotrophic factor (BDNF) and the neurotrophins (NT3 and NT4/NT5). Fibroblast growth factors (FGFs) constitute another large family of polypeptide growth factors that induce mitogenic, chemotactic, and angiogenic activity in a wide variety of cells, including neurons (Thomas, FASEB J. 1:434-440, 1987; Burgess et al., Ann. Rev. Biochem. 58:575-606, 1989; Moscatelli et al., U.S. Pat. No. 4,994,559). While the role of polypeptide growth factors in the developing animal has become increasingly evident, their role in the mature animal, particularly in the nervous system, is much less clear.
Injury or death of neurons in a mature animal produces motor and/or cognitive deficits that are often permanent. Patients who suffer a "stroke," or any other form of cerebral ischemic episode, usually recover partially, but often remain mildly to severely debilitated. Currently, aside from physical therapy, there is no treatment that reliably improves the prognosis of a patient who has suffered a cerebral ischemic episode.